The type and concentration of synthetic chemicals that are in our environment today are of greater concern to government, businesses, and society in general than in any time in history. Multiple factors contribute to this, such as national security concerns related to the use of deadly chemicals as weapons, the risk of an intentional or accidental chemical spill, environmental awareness, and increased concern of the potential impacts of such chemicals on human health. The range of applications for sensors that can accurately measure volatile gases is wide. For example, the Department of Homeland Security needs sensors to detect the presence of chemical weapons, such as chemical warfare agents; and explosives. These sensors can be integrated into traffic lights in large cities, as components of air-intake valves in municipal buildings, and used on-board devices for unmanned aerial vehicles or robotic vehicles that are used to explore hazardous situations. Similar sensors can be used to detect natural gas leaks for home and business owners and to monitor outdoor air in local communities, school playgrounds, or agricultural settings. Industrial manufacturers, on the other hand, need sensors to monitor facility air during production, survey product off-gassing, and assist with maintaining safe levels of permissible exposure limits (PELs) to protect workers against the health effects of exposure to hazardous substances including toxic industrial chemicals. Other industrial applications include monitoring product performance as in the case of interrogating vehicle emissions for release of volatile gases and assessing fruit ripeness based on volatile gas emissions. Another area for application of sensors is in the environmental monitoring for assessment of health effects related to long term exposure to volatile gases such as pesticides and aldehydes and in the arena of food freshness for indicators of spoilage.
There is also broad potential for use of sensors in biomedical applications. For example, sensors have been used to monitor the composition of gas mixtures used for anesthesia during surgical procedures or to monitor the exhaled gases to access the metabolic activities. Recently, analysis of human breath has emerged as a new non-invasive technique for diseases diagnosis. The exhaled human breath contains a number of volatile gases such as oxygen, carbon dioxide, nitrogen, carbon monoxide, acetone, ammonia, hydrogen sulfide, amines, oxides of nitrogen etc. (Manolis, 1983; Smith et al, 1999; and Diskin et al, 2003). Measurements of analytes in exhaled breath can be applied to a wide range of disease states, including diabetes (Henderson et al, 1952; Sulway et al, 1970; Crofford et al, 1977; and Novak et al, 2007) and gastrointestinal disorders (Perman, 1991; Bauer et al, 2000; and Nieminen et al, 2000), for which volatile biomarkers in patient breath have been identified. Nitric oxide (NO) is another analyte in exhaled breath and it can be used as a biomarker for asthma (Alving et al, 1993).
Twenty-two million people in the US have been diagnosed with asthma (CDC, 2008), yet the tools available for monitoring asthma are limited. A few simple tools are available for in-home use that can provide some indication of lung health. Peak flow meters, for example, can measure one's peak expiratory flow rate (PEFR), and spirometers can measure lung volume and flow. However, abnormal readings from either of these devices can be attributed to a variety of causes other than asthma, and these techniques may not be predictive of onset of an acute asthmatic attack, nor provide immediate feedback on the effect of a therapeutic intervention. A better approach is to monitor nitric oxide, a biomarker of asthma, which is exhaled in human breath. The concentration of fractional exhaled nitric oxide (FeNO) is higher in asthmatics than in healthy people. It increases during an asthmatic exacerbation, and decreases following treatment with an inhaled corticosteroid (Smith et al, 2004). A breath analyzer that reliably detects FeNO would allow widespread self-monitoring by the asthmatic population.
In 1991 Gustafsson et al demonstrated the presence of nitric oxide in the exhaled breath of humans. Shortly thereafter it was reported that FeNO levels are elevated in asthmatics compared to that in control subjects (Alving et al, 1993). Since the time of these discoveries there now exist over 1,000 publications (Medline search, December 2007) that implicate nitric oxide as a biomarker of airway inflammation and deliver a vast amount of knowledge on the importance of FeNO measurements. For example, nitric oxide levels in exhaled breath correlate with eosinophil-mediated airway inflammation (van den Toorn et al 2001, Mattes et al 1999, Jatakanon et al 1998). Several investigators have reported that nitric oxide concentrations decrease following use of corticosteroids (Massaro and Drazen; 1996, Yates et al 1995; Silkoff et al 1998; van Rensen, 1999) and that measurements of FeNO can be used as a noninvasive diagnostic for asthma (Pijnenburg, 2005). It has also been shown that FeNO measurements can be used to regulate medications (Smith et al, 2005; Taylor, 2006)
Levels of exhaled nitric oxide can provide feedback for asthma patients and their physicians. While numerous studies have been performed to measure levels of exhaled NO there is little consensus on what the standard level is in healthy subjects. In fact, physiological levels of NO can vary greatly between people. Some of the variability is related to age (Buchvald et al, 2005) and gender (Olivieri et al 2006). However, some of the NO variability can be attributed to the variety of test methods due to the lack of standardized procedures among the testing groups (Müller et al, 2005). None the less, studies report that the levels of FeNO in asthmatics are significantly higher than those in control subjects (Alving et al 1993, and Kharitonov et al, 1994). Several groups have established baseline levels of FeNO in asthmatics and monitored their levels during exacerbations. Jones et al (2001) reported that when steroids were withdrawn a 60% increase in FeNO over baseline predicted a loss of control in asthma 80-90% of the time. In a second study, Jones et al (2002) showed a positive correlation between serial measurements of FeNO and a dose-response to an inhaled steroid. Reports such as these indicate 1) the importance of establishing a baseline for each individual, and 2) that tracking an individual's FeNO levels can be extremely useful in predicting exacerbations and monitoring efficacy of medications.
One of the major problems in completing these assessments is the lack of methods and monitoring devices to measure components from exhaled breath. Several technologies exist that are capable of detecting and monitoring gas-phase compounds including those found in breath. The sensors available and their disadvantages are described here briefly. They are based on technologies that can be categorized into four main classes including: chromatography and spectrometry, electrochemical sensors, mass sensors, and optical sensors. Chromatography and spectrometry involve separation of complex mixtures by passing them over selectively absorptive materials and subsequent analysis of the components. These instruments are gas chromatographs, ion mobility and mass spectrometry (IMS) instruments, and photo-ionization (PIDs) and flame ionization detectors (FIDs). Instruments in this category are benchtop, portable, or miniature (lab on a chip) in size. The general deficiencies of such instruments are that they are prohibitively expensive and technically complicated, require recalibration, most lack portability, require GC for specificity, sensitive to humidity, and require on-board hydrogen gas. Electrochemical sensors detect changes in electrical current passed through an electrode when a chemical reacts with that electrode. Included in this category are polymer-absorption chemiresistors, catalytic bead sensors, metal-oxide semi-conductor sensors, single wall nanotubes (SWNT), and potentiometric and amperometric sensors. In general these instruments have selectivity issues, high drift, and short shelf-life, require internal pump and elevated temperatures for operation, are sensitive to water vapor and to hydrogen. Mass sensors, including surface acoustic wave sensors and microcantilever sensors, detect changes in the profile representing the mass of the chemical. They are prohibitively expensive, susceptible to humidity changes, and not readily transportable. Optical sensors, including fiber optic sensors, colorimetric, (chemical papers, detector tubes), and infrared sensors, detect changes in visible light when a chemical is present. They have limited dynamic range, lack specificity, high rate of false positives, optics impaired by particulates, and sensitive to humidity.
Although many sensors are capable of measuring gases and some are currently used in research applications, few have been adapted for use by the healthcare consumer. In general, hurdles to these sensor technologies include instrumentation that is expensive, requires frequent calibrations and regular maintenance, complicated to operate, large in size, and lacks selectivity for the targeted gas.
LCs have been previously used to detect gas phase compounds. These methods for detecting compounds with liquid crystals are based on reversible or nonreversible interactions between compounds and functional groups on a surface that can detect such interactions. This body of work relies on the interaction of the LC with a functionalized surface, i.e., surface driven detection. The surfaces may be treated with metals (gold, titanium), with self-assembled monolayers (e.g., MBA, MUA), ligands or recognition moieties (metal salt complexes or enzymes), and linkers (homo or hetero-bifunctional) that are used to immobilize the layers. Thus, the technology is first dependent on the fabrication of appropriately functionalized surfaces and secondly dependent on the diffusion of the analyte through the LC layer to the surface so that the interaction between the analyte and the surface may occur. In devices that rely on surface interactions, it is a change of the orientation of the LC pre and post-exposure to the analyte that is measured to determine whether the analyte is present.
What is needed in the art are assays for detection of gas phase compounds that do not rely on complex, expensive equipment or exclusively on the interaction of the analyte with the surface of the device.